ObjectiveTo investigate the levels of regulatory T cells (Treg) and FoxP3 gene in patients with gastric cancer before and after operation. MethodsTwenty patients with definite diagnosis of gastric cancer and 15 healthy volunteers were selected. The levels of Treg and T cell subsets in peripheral blood were determined by detecting of CD4 and CD25 with immunefluorescence stain and flow cytometry, the expressions of FoxP3 mRNA in these Treg were detected by RTPCR technique. The expression of FoxP3 protein in the gastric cancer tissue was measured by immunohistochemistry assay. ResultsThe percentage of Treg cells in total CD4+ T isolated from the patients with gastric cancer was higher than that of healthy volunteers 〔(19.39±5.58)% versus (9.91±3.23)%, Plt;0.01〕, and it markedly decreased after operation 〔（13.50±5.93）% versus (19.39±5.58)%, Plt;0.05〕. The FoxP3 mRNA expression in the patients with gastric cancer was also higher than that of healthy volunteers (0.86±0.03 versus 0.64±0.02, Plt;0.01), and decreased after operation (0.73±0.04 versus 0.86±0.03, Plt;0.05). The percentage of CD4+T cell in mononucleocytes of peripheral blood of patients with gastric cancer was significantly lower than that of healthy volunteers (Plt;0.01), but the difference was not significant between before and after operation. FoxP3 protein expressed in cytoplasm of 13 patients with gastric cancer, in which bly positive in 2 cases, middle positive in 6 cases, weakly positive in 5 cases. FoxP3 protein didn’t express in cytoplasm of 7 patients with gastric cancer. ConclusionsTreg may have a significant effect on the onset and development of gastric cancer through immunosuppressive effect. Tumor tissue is an important initiating agent on Treg proliferation.
Objective To summarize the clinical characteristics of pneumocystis pneumonia (PCP) secondary to interstitial lung disease (ILD) to improve the prophylaxis and management level of clinicians. Methods The clinical data of 50 patients with PCP secondary to ILD in the Department of Respiratory and Critical Care Medicine of Nanjing Drum Tower Hospital from January 2015 to December 2022 were collected. SPSS 26.0 software was used for statistical analysis. Results A total of 50 patients with PCP secondary to ILD were screened. Among the 50 patients, there were 23 males and 27 females, with a median age of 64 years old. Forty-eight cases (96%) had a history of glucocorticoid therapy with the median duration of 3 months; 31 (77.5%, 31/40) cases developed PCP in the first 6 months after glucocorticoid therapy; 34 cases had a history of glucocorticoid and immunosuppressants at the same time. None of the 50 ILD patients used drugs for PCP prophylaxis before developing PCP. The major clinical manifestations of PCP secondary to ILD were worse cough and shortness of breath or fever. Laboratory results showed 38 cases (76.0%) had peripheral blood total lymphocyte count <200/µL, 27 cases (54.0%) had CD4+ T cell count <200/µL, 34 cases (68.0%) had CD4+ T cell count <300/µL, 37 cases (74.0%) had CD3+ T cell count <750/µL, 34 cases (68.0%) had β-D-glucan test >200 pg/mL, 35 cases (70.0%) had lactic dehydrogenase > 350 U/L and 41 cases (82.0%) had type Ⅰ respiratory failure. High resolution computed tomography showed added ground-glass opacity and consolidation on the basis of the original ILD. Thirty-six cases were detected the Pneumocystis jirovecii by metagenomic next-generation sequencing with broncho-alveolar lavage fluid as the main source, and 2 cases by smear microscopy. All patients were treated with trimethoprim-sulfamethoxazole. After treatment, 29 cases were discharged with a better health condition, 10 cased died, and 11 cases left hospital voluntarily because of treatment failure or disease deterioration. Conclusions After the use of glucocorticoid and immunosuppressants, ILD patients are susceptible to life-threatening PCP. It is particularly important to make an early diagnosis. Attention should be paid to integrate the symptoms, levels of peripheral blood lymphocyte count, β-D-glucan test, lactic dehydrogenase and imaging findings to make an overall consideration. It is suggested to perform next-generation sequencing with broncho-alveolar lavage fluid at an early stage when patients can tolerate fiberoptic bronchoscopy to avoid misdiagnosis and missed diagnosis. ILD patients often develop PCP in the first 6 months after using glucocorticoid and immunosuppressants. During follow-up, peripheral blood CD4+ and CD3+ T cell count should regularly be monitored so as to timely prevent PCP.
ObjectiveTo analyze the relation between regulatory T cell (Treg)/ helper T cell 17 (Th17) imbalance and the pathogenesis of acute pancreatitis (AP) and to explore the relation between Treg/Th17 cell imbalance and helper T cells 1, helper T cells 2 and cytokines in patients with AP, so as to provide a new therapeutic target for immunotherapy of AP. Methods From January to December 2020, 40 patients diagnosed with AP ( AP group) in The People’s Hospital of Xinjiang Uygur Autonomous Region and 40 healthy subjects who underwent physical examination (normal control group) during the same period in this hospital were selected as the research objects. Their peripheral bloods were collected and the proportion of Treg and Th17 cells was detected by flow cytometry. Plasma levels of interleukin-10 (IL-10) and interleukin-17 (IL-17) were detected. Results Compared with the normal control group, the proportions of Treg and Th17 cells increased before treatment in the AP group, the differences were statistically significant (t=5.78, P<0.001; t=5.82, P<0.001). The levels of IL-10 and IL-17 increased, the differences were statistically significant (t=7.14, P<0.001; t=35.22, P<0.001). After treatment, the AP group as compared with the normal control group, the proportions of Treg and Th17 cells increased but the differences were not statistically significant (t=1.87, P>0.05; t=0.29, P>0.05), the level of IL-10 increased and the difference was statistically significant (t=3.98, P<0.001), the level of IL-17 increased but the difference was not statistically significant (t=1.67, P>0.05). After treatment as compared with before treatment in the AP group, the proportions of Treg and Th17 cells decreased, the differences were statistically significant (t=3.07, P<0.01; t=4.99, P<0.001). The levels of IL-10 and IL-17 decreased, the differences were statistically significant (t=3.38, P<0.001; t=30.63, P<0.001). Conclusion In AP, Treg cells mediate immunosuppression and Th17 cells mediate inflammatory response, promoting the occurrence and development of inflammation in the disease. IL-10 and IL-17 may play an important role in regulating their differentiation and homeostasis.
Objective To summarize research progress of the mechanism of natural killer cells (NK cells) acted in regulating the T cell immunity in chronic infectious disease. Method Literatures about recent studies concerning how NK cells act as a regulator for T cells in chronic infectious disease were reviewed according to the results obtained from PubMed, Embase, CNKI, CBM, and Wanfang databases. Results NK cells that acted as regulators of T cell immunity could affect T cell immune responses through influencing antigen presentation, secreting cytokine, and presenting lytic activities, thus playing an important role in the immunological therapy of chronic infectious diseases. Conclusion NK cells are critical for T cell immune regulation, which could provide noval strategies for immunological therapy of chronic infectious disease, transplantation-related immune rejection, and autoimmune disease.
Objective To investigate the efficacy of continuous blood purification ( CBP) in the treatment of severe sepsis, and explore the related immune regulatory mechanisms. Methods Forty-eight patients with severe sepsis were randomly divided into a control group ( n =23) and a CBP group ( n =25) .CD4 + CD25 + regulatory T cells ( Treg% ) in peripheral blood and APACHEⅡ score were measured dynamically before treatment and 12, 24, 36, 48, 60, 72 hours after treatment. Meanwhile the length of ICUstay, duration of mechanical ventilation, and 28 day mortality were determined. Results Compared with the control group, the length of ICU stay, ventilator time, incidence of multiple organ failure, and mortality decreased significantly in the CBP group ( P lt; 0. 05) . And CBP also decreased Treg% and APACHEⅡ score significantly. There was a positive correlation between Treg% and APACHEⅡ score ( r =0. 804, P lt;0. 01) .Conclusion Early CBP treatment can reduce Treg%, improve cellular immunity and improve the prognosis of sepsis.
ObjectiveTo investigate the application value of tuberculosis T cell test (T-SPOT.TB) in the clinical diagnosis of children's tuberculosis. MethodsThe children were selected from Anti-TB Institute of Shantou and the Second Affiliated Hospital of Shantou University from March to December, 2012; they were classified into 4 groups:tuberculosis group (112 cases), non-tuberculosis group (58 cases), high risk of tuberculosis group (60 cases) and healthy control group (60 cases). In each group, the T-SPOT.TB, tuberculin test (PPD), tuberculosis antibody detection (TB-DOT), the sputum smear acid fast stain, and the sputum mycobacterium tuberculosis culture were performed. The sensitivity and specificity of each clinical testing method was compared. The statistical analysis was also performed in the tuberculosis group according to subsection grouping:negative/positive tuberculosis culture, the in-pulmonary/extrapulmonary tuberculosis and the normal immune/immunodeficiency hosts. ResultsIn the tuberculosis group, the T-SPOT.TB has a diagnostic positive rate of 92.9%, significantly higher than that of other clinical testing methods (χ2=9.33, P<0.01; χ2=81.71, P<0.01; χ2=142.00, P<0.01; χ2=101.71, P<0.01). In the non-tuberculosis group, the T-SPOT.TB has a false diagnostic positive rate of 3.4%, a little higher than that of sputum smear and sputum culture, but similar to that of TB-DOT, and much lower than that of PPD test (27.6%; χ2=12.89, P<0.01). In the high risk of tuberculosis group, the T-SPOT.TB has a diagnostic positive rate of 25.0%, higher than that of TB-DOT, sputum smear and sputum culture (P<0.05). In the healthy control group, the T-SPOT.TB has a specificity of 95.0%, significantly higher than that of PPD test (71.7%; χ2=11.76, P<0.01). T-SPOT.TB has a good sensitivity in all of the subsection groups:negative/positive tuberculosis culture, the in-pulmonary/extrapulmonary tuberculosis and the normal immune/immunodeficiency hosts (P>0.05). The total coincidence rate of T-SPOT.TB with the PPD test result was 78.6%. ConclusionT-SPOT.TB has a relatively higher sensitivity and specificity in the diagnosis of children's tuberculosis. With objective and accurate results and less interference factors, it shows a relatively higher clinical application value in the diagnosis of children's tuberculosis.
Objective To explore the operative safety of HIV-infected patients with colorectal cancer in different degrees of immunodeficiency. Methods A total of 56 patients, including 26 cases of HIV positive (HIV-positive group) and 28 cases of HIV negative (HIV-negative group), who underwent radical operation for colorectal cancer between January 2012 and December 2015, were enrolled in our study. We divided HIV-positive patients into three groups according to CD4+ T cells count in peripheral venous blood before 1 day (D0) of the surgery (HIV-positive Ⅰgroup with CD4+ T cells count >500/μL, HIV-positive Ⅱgroup with CD 4+ T cells count among 200–500/μL, and HIV-positive Ⅲ group with CD4+ T cells count <200/μL). Non-infective patients were enrolled in HIV-negative group. Leukocyte count, neutrophil percentage, lymphocyte percentage, CD 4+ T cells subsets count, and CD8+ T cells subsets count of the 4 groups in different time points were tested. In addition, we compared postoperative complications, carcinoembryonic antigen (CEA), and postoperative survival rate between the HIV-positive group and the HIV-negative group. Results In 56 cases, there were 26 cases of HIV-positive patients (including 10 cases of HIV-positive Ⅰ group, 8 cases of HIV-positive Ⅱ group and 10 cases of HIV-positive Ⅲ group). Variance results about repeated measurement data showed that, variation of leukocyte count, neutrophil percentage, lymphocyte percentage, and CD8+ T cells count among 4 groups after surgery had no statistical significance (P>0.05), in addition there was no significant on time effect and interactive effect of time and group (P>0.05). CD4+ T cells count in the 4 groups showed a trend from decline to rising with time going, and the time effect had statistical significance (P<0.05). The speed and amplitude of decline and recovery of CD4+ T cells count were different among groups, and the group effect had statistical significance (P<0.05). CEA showed a trend of decline after surgery in both HIV-positive group and HIV-negative group, and the time effect had statistical significance (P<0.05), but the group effect and interactive effect of time and group had no statistical significance (P>0.05). No statistically significant differences in amount of blood loss, duration of surgery, postoperative stay, nor complication rate (including incision infection, pulmonary infection, and opportunistic infections after surgery) were found between the HIV-positive group and the HIV-negative group (P>0.05). The overall survival situation of the HIV-positive group and the HIV-negative group had no statistical significance (P>0.05). Conclusions Radical operation for HIV-infected patients with colorectal cancer has an impact of " first inhibition and recovery” on cellular immunity over a period of time. Incidence of postoperative complications and survival rates are similar in HIV-positive patients and HIV-negative patients. In a word, it’s safe to have radical operation for colorectal cancer in HIV-positive patients under the proper perioperative treatment.
Objective To investigate the suppression effect and mechanism of Astilbin on lung allograft rejection in rats, in order to know the function of Astilbin on rats’ lung acute rejection. Methods The model of rat left lung transplantation was set up. Sixty lung transplanted rats were divided into two groups randomly, control group: rats were fed with normal saline 1ml per day, experimental group: rats were fed with Astilbin 1mg/kg per day. Survival time, transforming rate of T cells in spleen, activity of interleukin 2 (IL-2) in spleen lymph cells and apoptosis of T cells were observed. Changes in ultrastructure of pulmonary arteries were observed by electron microscope. Results The survival time in experimental group was prolonged than that in control group (25.4±2.1 d vs. 13.4±1.2 d;t=2.042, Plt;0.05）. Transforming rate of T cells of spleen in experimental group was significant lower than that in control group (23 465.8±8 783.4 cpm vs. 74 567.3±12 874.6 cpm; t=2.284，Plt;0.05）.Activity of IL-2 of spleen lymph cells in experimental group was significant lower than that in control group (425±2.65U/ml vs. 23.46±1.82U/ml; t=3.165, Plt;0.01).Effectively derive apoptosis of activated T cells in acute rejection were observed in experimental group, the ultrastructure of pulmonary arteries showed attenuated injury in experimental group. Conclusion Astilbin decreased the IL-2 concentration in plasma and induced the apoptosis in activated T cells, then suppressed the acute rejection of lung allograft and prolonged the survival period of lung transplantation rats.
ObjectiveTo improve clinicians' understanding of severe cytokine release syndrome (CRS) through reporting the clinical manifestation, diagnosis, treatment, and prognosis of CRS after chimeric antigen receptor T (CAR-T) cell therapy in a patient with solid tumor. Methods A patient with ovarian cancer who suffered severe CRS after CAR-T cell therapy in the Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University was reviewed. Relevant studies were searched for literature review. Results The patient, a 55-year-old woman, was diagnosed with ovarian cancer in early 2016 and continued to progress despite multiple lines of treatment, so she received CAR-T cell therapy on September 16, 2022. The patient developed a fever 2 days after infusion, and developed dyspnea and shortness of breath with oxygen desaturation 2 days later. Her condition kept deteriorating with respiratory distress and severe hypoxia 6 days after infusion, and the level of interleukin-6 and interferon-gamma continued to be elevated. Chest CT showed pleural effusion and massive exudation of both lungs. Considered to have acute respiratory distress syndrome (ARDS) due to severe CRS, she was transferred to the intensive care unit (ICU). The patient was treated with tocilizumab, high-dose intravenous glucocorticoid pulses, mechanical ventilation, and sivelestat sodium for ARDS. Her symptoms were gradually relieved, and the results of laboratory tests were gradually stabilized. The patient was extubated 6 days after ICU admission and discharged from ICU a week later. Six patients were screened out with ARDS or acute respiratory failure caused by CRS after CAR-T cell therapy, whose treatments were mainly anticytokine agents combined with high-flow oxygen therapy or invasive mechanical ventilation. One of them died. ConclusionsClinicians should be alert to severe CRS during the administration of CAR-T cell. Rapid interruption of the inflammation development is the key to all treatments. If respiratory and/or circulatory dysfunction occurs, patients should be transferred to ICU in time for organ support therapy.
ObjectiveTo investigate the proportion of peripheral blood CD4+CD25+ regulatory T cells (Tregs) in patients with pancreatic head carcinoma, the dynamic changes of these cells before and after pancreatoduodenectomy were also analyzed. MethodsThe proportions of peripheral blood CD4+CD25+ Tregs in patients with pancreatic head carcinoma and normal individuals were examined by using flow cytometric analysis. The CD4+/CD8+ ratio was also studied before and after operation. ResultsThe patients with pancreatic head carcinoma showed higher ratio of CD4+CD25+ and CD4+CD25high Tregs compared with normal control before operation (Plt;0.05). However, the percentage of these T cells reduced significantly after pancreatoduodenectomy, which was most obviously on the 3rd day after operation (Plt;0.01, Plt;0.05). After operation, CA199 level began to decrease, which was obvious on the fourteen day after operation. This tendency of CD4+CD25high Tregs changes was similar to that of CA199. The patients showed an decreased ratios of CD4+/CD8+ compared with normal controls, which further declined after operation, and reached the lowest point on the seventh day after operation (Plt;0.05). ConclusionsPancreatoduodenectomy may be helpful for the recovery of antitumor immunity. The perioperative period of patients with pancreatic head carcinoma may be a beneficial windowphase for immune intervention and Tregs may be served as target cells.